My long-term career goals are to become successful independent investigator with expertise on alcohol-induced changes in the immune system, to develop a well-funded laboratory and train future alcohol researchers. Alcohol abuse is associated with suppression of both of innate and adaptive immune systems leading to more infections, greater susceptibility to cancer and delayed recovery from trauma. The long-term goal of this work is to elucidate the mechanisms by which alcohol impairs immune function so therapeutic agents can be developed to reverse these effects. The overall hypothesis is that alcohol consumption inhibits immune function via DC dysfunction. To test this, the extent of alcohol inhibition on both local and systemic immunity will be compared using two different approaches. In the first, the effect of chronic ethanol consumption on DC phenotype and function will be determined in the liver and skin as well as in their corresponding draining lymph nodes. The second approach will differentiate the functional effects of alcohol on resident lymph node DC and migrating DC that come to lymph nodes from peripheral tissue. My desire to refocus my research on the mechanisms by which alcohol causes immune suppression has been enhanced the opportunities at the University of Pittsburgh where successful collaborators and mentors are available in both immunology and alcohol research. This career development award will provide me the protected time that I need to establish sufficient background to position myself to become an independently funded researcher in the area of alcohol-induced immunological changes. The career development plan consists of three major components: coursework training in immunology and statistics, professional development training, and training in new research techniques. Furthermore, this award will give me the opportunity to establish a publication record in the interrelationship between alcohol consumption and immunology so I can become competitive enough to receive my first R01. PUBLIC HEALTH RELEVANCE: The goal of this work is to gain sufficient understanding of the mechanisms associated with ethanol related immune suppression that therapies can be designed to reverse this detrimental effect of alcohol usage.